Targeting FGFR1-amplified lung squamous cell carcinoma with the selective pan-FGFR inhibitor BGJ398.

• DOI: 10.1200/jco.2014.32.15_suppl.8034
• Publication Date: 2019-01-03T22:36:54Z
• Authors: Lucia Nogova; Lecia V. Sequist; Philippe Alexandr...; Manuel Hidalgo; Jean-Pierre Delord; Martin H. Schuler; Wan-Teck Lim; D. Ross Camidge; Reinhard Buettner; Lukas Carl Heukamp; Masyar Gardizi; Matthias Scheffler; Kato Kambartel; Francois Philippe...; Suman Sen; Randi Isaacs; Maud Joannaert; Caroline Lefebvre; Juergen Wolf
• Keywords: CISH

8034 Background: Identifying molecular drivers in lung squamous cell carcinoma (SCC) is a major medical need since no targeted therapy available yet for this subtype. Fibroblast growth factor receptors (FGFRs) are physiologically involved proliferation and survival. Genetic alteration of FGFR genes leads to deregulated activation various cancers, FGFR1 amplification has been detected SCC. Here, we report on patients (pts) with FGFR1-amplified SCC treated phase 1 study BGJ398, potent, selective pan-FGFR inhibitor. Methods: While dose-escalation enrolled pts ≥ 18 years age any genetically altered tumor, here the subgroup advanced or metastatic 100 125 mg BGJ398 once daily 28-day cycles. Pts who had progressed following at least line therapy, including platinum, were eligible enrollment. tumors identified by fluorescent/chromogenic situ hybridization (FISH/CISH) using, most pts, score recently established (Schildhaus, Mod Path 2012). Radiologic evaluation was performed every 8 weeks. Results: As November 22, 2013, 21 maximum tolerated dose mg/day (n = 19) 2). Screening commonly locally 17) vs centrally 4) assayed FISH all but case (CISH). Of 17 evaluable data cutoff, 2 achieved partial responses (PR; confirmed RECIST). PRs durable, lasting about 3 months, respectively. note, additional PR (1 confirmed) after cutoff date. Additionally, stable disease tumor regressions noted (up 11% reduction). The adverse event profile included manageable reversible hyperphosphatemia, as well stomatitis, alopecia, decreased appetite, fatigue. Conclusions: Here first molecularly demonstrating clinical efficacy. These encourage further development efforts optimize predictive biomarkers inhibitor sensitivity. Clinical trial information: NCT01004224.